The objective of this project is to prove the feasibility of the research plan for Phase II of this DHHS/SBIR program to demonstrate a large cost reduction for the in vitro production of monoclonal antibodies. According to the Company's system, hybridomas are immobilized in hydrocolloid gels or in extended open foam carriers, both in the form of 0.1-0.5 mm beads, and cultured as a thick slurry in a fluidized bioreactor. The Company already has this technology well developed for yeast and bacteria cells. The technical objective of the Phase II SBIR research program is to optimize hybridoma culture with this system for minimum cost of purified antibody product. The commercial objective is to enable the Company to manufacture for sale laboratory and production hybridoma-culture systems and also to produce low-cost monoclonal antibodies as a contract manufacturer. The first scientific objective is to understand the biological variables which control antibody productivity (mg/day/reactor volume), yield (mg/l of media consumed) and antibody concentration (mg/ml). A second scientific objective is to establish the basis for optimizing serum-free nutrient media and immobilization materials and methods to minimize overall cost of culivation and purification. The third objective is to establish means to minimize cell growth under steady-state continuous culture without inhibition of immunoglobulin production, so as to maximize yield of product and minimizing the rate of genetic alteration in the culture.